Functional expression of transient receptor potential vanilloid-related channels in chronically hypoxic human pulmonary arterial smooth muscle cells.

Transient receptor potential vanilloid (TRPV) channels are nonselective cation channels pertinent to diverse physiological functions. Multiple TRPV channel subtypes have been identified in different tissues and cloned. The aim of this study was to investigate the role of TRPV channels in hypoxia-induced proliferation of human pulmonary artery smooth muscle cells (PASMCs) and its possible signal pathway. Reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, and Western blot analysis were used to detect the expression of TRPV in human PASMCs. Cell number was determined with a hemocytometer. Cytosolic Ca2+ concentration ([Ca2+]cyt) was measured with a dynamic digital Ca2+ imaging system. The mRNA of TRPV1-4 was detected in human PASMCs and chronic hypoxia up-regulated expression levels of the TRPV1 gene and protein. The ability to proliferate, the resting [Ca2+]cyt, and cyclopiazonic acid-induced capacitative Ca2+ entry in human PASMCs were enhanced significantly by chronic hypoxia compared with the control, and these effects were inhibited in a dose-dependent manner by capsazepine, a TRPV1 channel inhibitor. These results suggest that TRPV1 may be a critical pathway or mediator in chronic hypoxia-induced proliferation of human PASMCs.